Obesity has become a worldwide problem. Medical and nutrition experts have been paying much attention to the problem and trying to find solutions. Decreasing appetite and food intake and maintaining low food intake are considered effective ways to deal with the obesity problem. Accordingly, many nutraceuticals providing satiety are developed.
Satiety is controlled by many factors, among which neuropeptides are of significant importance. Cholecystokinin (CCK), a group of neuropeptides secreted by mucosal cells of intestine, has been shown to promote release and secretion of digestive enzymes from gallbladder and pancreas into intestine and produce satiety signals, which can inhibit desire for food intake.
CCK is produced by intestinal I cells within the intestinal mucosa (Buchan et al., Gut, 1978, 19:403-407). The intestinal I cells have a roughly triangular shape with their apical surface oriented toward the intestinal lumen of the intestine and secretary granules containing CCK concentrated around the base. The orientation allows the cells to be stimulated by nutrients and release CCK into the blood and/or surrounding tissue (Moran and Kinzig, Am. J. Physiol. Gastrointest. Liver Physiol., 2004, 286:G183-G188). CCK must binds to receptors located in gastric and duodenal vagus to induce a series of physiological activity (Moran et al., Am. J. Physiol. Regul, Integr. Comp. Physiol., 1997, 272:R1245-R1251). Furthermore, CCK receptors are also found in central nervous system. Therefore, CCK influences not only digestion but also secretion of other neurohormones, interacting with CCK to influence food intake (Woods, Am. J. Physiol. Gastrointest. Liver Physiol., 2004, 286:G7-G13). For example, Gutzwiller et al. reported the interaction between CCK-33 and glucagons-like peptide-1 (GLP-1) in inhibiting food intake and appetite in men (Gutzwiller et al., Am. J. Physiol. Regul. Integr. Comp. Physiol., 2004, 287:562-567). Moreover, CCK is a neuropeptide that produces satiety signals and is found to have interactions with adiposity signal leptin or insulin (Bado et al., Nature, 1998, 394:790-793; Brzozowski et al., Eur. J. Pharmacol., 1999, 374:363-376; Gallmann et al., Peptides, 2005, 26:437-445; Morton et al., J. Clin. Invest., 2005, 115:703-710). In view of the above, CCK plays an important role in food intake of animals.
It was found that many nutrients in food had CCK secretion inducing effect, especially proteins and lipids. Low carbohydrate diet, or Atkins diet popular in Western countries, was developed on the basis of the theory However, research has revealed that proteins and lipids are more effective in promoting CCK secretion in animals if they are in the form of peptides and fatty acids. For example, Nishi et al. demonstrated in 2001 that peptic hydrolysates of proteins stimulated CCK release (Nishi et al., Exp. Biol. Med., 2001, 226:1031-1036). In that study, they examined the direct effects of peptic hydrolysates of naturally occurring dietary proteins and found that hydrolysate of soybean protein isolate was the most effective in stimulating CCK release. Moreover, they found that the most bioactive peptide was the soybean β-conglycinin β51-63 fragment (Nishi et al., J. Nutr., 2003, 133:352-357). The amino acid composition and hydrophobicity of peptides may have to do with their CCK secretion inducing effect (Furuse et al., Comp. Biochem. Physiol., 1991, 99A:449-451; Backus et al., Regul. Pept., 1997, 72:31-40). Bernard et al. demonstrated that peptones stimulated intestinal cholecystokinin gene transcription via cyclic adenosine monophosphate response element-binding factors (Bernard et al., Endocrinology, 2001, 142:721-729).
JP2004010569 discloses an arginine-containing peptide having a CCK secretion promoting activity. The peptide is obtained by the decomposition of purified soybean β-conglycinin with a pepsin and is soybean β-conglycinin β 51-63 fragment. However, the starting materials used in JP2004010569 must be pretreated through complex purification steps and, accordingly, is more cost-ineffective. Therefore, there still exists a need for a more efficient and cost-effective method of producing peptides having a CCK secretion promoting effect.
Surprisingly the inventors discovered that one could treat soybean residues, which need not be pre-purified, with proteases to obtain peptides having a CCK secretion promoting activity. The peptide can increase satiety of animals so as to decrease their food intake and achieve the effect of weight control.